In the video, he is not assuming $\frac{du}{dx}$ is small. It has a definite nonzero value. He is taking the limit as $\Delta x$ gets small (goes to zero, or becomes an infinitesimal $dx$).
That expression
$$\lim_{\Delta x \rightarrow 0} \frac{1}{\Delta x} \left[\frac{du}{dx}_{(x+\Delta x)} -\frac{du}{dx}_{(x)} \right]
$$
is the very definition of the derivative, so it becomes:
$$ \frac{d}{dx} \left(\frac{du}{dx}\right)$$ or
$$ \frac{d^2u}{dx^2}$$
EDIT: Regarding your question on the "small slopes" assumption, small $du/dx$ does not necessarily mean small $d^2u/dx^2$. Taking a numerical example, you could imagine a sawtooth-like function whose slope $du/dx$ oscillates from $-0.1$ to $0.1$ over a $\Delta x$ of 0.01, which means its $d^2u/dx^2$ in that vicinity is 20.
In the vibrating string example, the "small slopes" assumption means that horizontal (x direction) motion of points on the string are negligible. Otherwise if you tried to pull the string up say to 45°, the string would have to change length or the endpoints would have to move, and the restoring force might not be linear, invalidating the simple wave model.